1-111450201-G-T

Variant names:

• chr1-111450201-G-T
• rs1264898
• NM_001688.5:c.77+328G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001688.5(ATP5PB):​c.77+328G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,000 control chromosomes in the GnomAD database, including 16,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16038 hom., cov: 32)
• Consequence: ATP5PB NM_001688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 17 publications found

Genes affected

ATP5PB (HGNC:840): (ATP synthase peripheral stalk-membrane subunit b) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5	c.77+328G>T		intron_variant	Intron 2 of 6	ENST00000369722.8	NP_001679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PB	ENST00000369722.8	c.77+328G>T		intron_variant	Intron 2 of 6	1	NM_001688.5	ENSP00000358737.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68265 AN: 151882 Hom.: 16019 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.427

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.450 AC: 68333 AN: 152000 Hom.: 16038 Cov.: 32 AF XY: 0.456 AC XY: 33868 AN XY: 74280

African (AFR) AF: 0.520 AC: 21526 AN: 41424

American (AMR) AF: 0.317 AC: 4839 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 998 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3851 AN: 5182

South Asian (SAS) AF: 0.616 AC: 2967 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4779 AN: 10544

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28084 AN: 67962

Other (OTH) AF: 0.425 AC: 898 AN: 2112

Alfa AF: 0.400 Hom.: 9816

Bravo AF: 0.437

Asia WGS AF: 0.607 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1264898; hg19: chr1-111992823;